Incidence and survival in patients with pharyngeal cancer in northern Finland

A population-based survey was conducted in northern Finland in order to study the incidence rate and survival in patients with pharyngeal cancer diagnosed between 1986 to 1996. A total of 95 new patients with hypopharyngeal, oropharyngeal or nasopharyngeal cancers were identified. The overall age-adjusted incidence rates (per 100,000 years) were 1.28 in men and 0.60 in women, giving an overall incidence rate of 0.89. Most of the tumours were diagnosed at stage IV, and the median disease-specific survival times were 27.6 months for the patients with oropharyngeal cancer, 13.5 months for nasopharyngeal cancer and 17.7 for hypopharyngeal cancer. The most important factors that were associated with a poor prognosis were stage IV in oropharyngeal [Hazard ratio (HR) 3.68, 95% confidence interval (CI) 0.97-13.92] and hypopharyngeal cancer (HR 3.99, CI 1.51-10.67) and age over 65 years in nasopharyngeal cancer (HR 9.28, CI 1.79-47.99).     

Molecular genetics of neuronal ceroid lipofuscinoses.

This overview describes recent advances in molecular biology of neuronal ceroid lipofuscinoses (CLN). Despite intensive research during last 20 years, the basic defects of these autosomal recessive-progressive encephalopathies of childhood remain unknown. Consequently, no specific cure is available. Methods of positional cloning (reverse genetics) starting from random linkage approach have been applied to search for gene defects in the infantile and juvenile forms of the disease. The results of this random search for disease loci have for the first time revealed molecular heterogeneity of CLN diseases. The gene defect causing the infantile form has been assigned to 1p32 in the Finnish family material, whereas the disease locus of the juvenile form has been localized to 16p12 in European and Canadian families. Finally, the gene defect causing the late infantile form has been excluded from both 1p32 and 16p12 chromosomal regions, referring to a third, still unknown locus causing CLN disease. Consequently, reliable prenatal and carrier diagnostics have now become possible in families with the infantile and juvenile forms of the disease, and DNA-based prenatal diagnostics have been successfully applied in the infantile form. Most importantly, the assignment of gene loci has brought these fatal brain diseases within the reach of molecular cloning strategies that eventually will result in revealing both the infantile and juvenile CLN genes and in identifying corresponding gene products.     

Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program

The NTP has a long history of using Fischer rats and has compiled a large database of incidences of lesions seen in control animals. Such a database is lacking for Harlan Sprague-Dawley (SD) rats. The intention of this paper is to report spontaneous lesions observed in female vehicle control Harlan SD rats, and to compare the incidence in 2 strains of rats (Fischer and Harlan SD) used in NTP studies. Female Harlan SD rats served as the test animals for a special series of 2-year studies. Male rats were not used in these studies. Complete histopathology was performed on all animals, and the pathology results underwent comprehensive NTP pathology peer review. The most commonly observed neoplasms in these female control Harlan SD rats were mammary gland fibroadenoma (71%), tumors of the pars distalis of the pituitary (41%) and thyroid gland C-cell tumors (30%). Female Fischer rats had incidences of 44% for mammary gland fibroadenomas, 34% for tumors of the pars distalis, and 16% for thyroid gland C-cell tumors. Fischer rats had a 15% incidence of clitoral gland tumors, while the Harlan SD rats had an incidence of < 1%. In contrast to Fischer F344 rats, the Harlan SD rats had a high incidence of squamous metaplasia of the uterus (44.2%). Squamous metaplasia is not a lesion commonly observed in NTP control Fischer rats. The Harlan SD rats had a very low incidence of mononuclear cell leukemia (0.5%), compared with an incidence of 24% in female Fischer rats.     

The effect of erythromycin, fluvoxamine, and their combination on the pharmacokinetics of ropivacaine

We studied the effect of fluvoxamine and erythromycin on the pharmacokinetics of ropivacaine in a double-blinded, randomized, four-way cross-over study. Eight healthy volunteers ingested daily 1500 mg erythromycin for 6 days, 100 mg fluvoxamine for 5 days (Days 2-6), both erythromycin and fluvoxamine, or placebo. On Day 6, each subject received a single dose of 0.6 mg/kg ropivacaine IV over 30 min. Ropivacaine, 3-hydroxyropivacaine, and 2',6'-pipecoloxylidide in venous plasma and urine samples were measured for up to 12 h and 24 h, respectively. Fluvoxamine increased the area under the drug plasma concentration-time curve (AUC) of ropivacaine 3.7-fold (P: < 0.001), prolonged the elimination half-life (t(1/2)) from 2.3 to 7.4 h (P: < 0.01), and decreased the clearance by 77% (P: < 0.001). Erythromycin alone had only a minor effect on the pharmacokinetics of ropivacaine. However, when compared with fluvoxamine alone, the combination of fluvoxamine and erythromycin further increased the area under the drug plasma concentration-time curve and t(1/2) of ropivacaine by 50% (P: < 0.01). We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces elimination of ropivacaine. Concomitant use of fluvoxamine and CYP3A4 inhibitor erythromycin further increases plasma ropivacaine concentration by decreasing its clearance. Implications: Clinicians should be aware of the possibility of increased toxicity of ropivacaine when used together with inhibitors of CYP1A2. Concomitant use of CYP1A2 and CYP3A4 inhibitors further increases ropivacaine concentration.     

Physiological instability is linked to mortality in primary central nervous system lymphoma: A case–control fMRI study

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG_BOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age‐matched controls (median 63y; 73% females) were scanned for MREG_BOLD signal during 2018–2021. Motion effects were removed. Voxel‐by‐voxel Coefficient of Variation (CV) maps of MREG_BOLD signal was calculated to examine the stability of physiological brain pulsations. Group‐level differences in CV were examined using nonparametric covariate‐adjusted tests. Subject‐level CV alterations were examined against control population Z‐score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast‐enhanced, diffusion‐weighted, fluid‐attenuated inversion recovery (FLAIR) data]. Whole‐brain mean CV was linked to short‐term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10⁵mm³) extended spatially beyond FLAIR lesions (median 0.62 × 10⁵mm³) with differences in volumes (p = .0055).     

Slow vasomotor fluctuation in fMRI of anesthetized child brain

Signal intensity changes in fMRI during rest caused by vasomotor fluctuations were investigated in this work. Resting‐state baseline fluctuations were evaluated in 12 children anesthetized with thiopental. Five subjects had fluctuations related to subvoxel motion. In seven subjects without significant motion, slow signal fluctuation at 0.025–0.041 Hz near one or more primary sensory cortices was observed. In each subject the amplitude and frequency of the fluctuations were stable. It is hypothesized that thiopental, which reduces blood pressure and flow in the cortex, alters the feedback in neurovascular coupling leading to an increase in the magnitude and a reduction in the frequency of these fluctuations. The use of anesthesia in fMRI may provide new insight into neural connectivity and the coupling of blood flow and neural metabolism. Magn Reson Med 44:373–378, 2000. © 2000 Wiley‐Liss, Inc.     

Lateral release and proximal realignment for patellofemoral malalignment: A prospective study of 40 knees in 36 adolescents followed for 1-8 years

We performed lateral release and proximal realignment for painful patellofemoral malalignment in 36 adolescents (40 knees), with a mean age of 14 (9-16) years. The mean follow-up was 4 (1-8) years. The subjective outcome was excellent in 20 knees, good in 13, fair in 5, and poor in 2. The mean radiographic correction of the lateral patellar shift was 75%, and of the tilting angle of the patella 27%. There was a positive association between the realignment effect and the subjective outcome.     

Increased incidence of Hirschsprung's disease in patients with hypoplastic left heart syndrome—a common neural crest-derived etiology?

Background

The enteric ganglions and the outflow tract of the heart originate from the neural crest. Impaired migration or differentiation of the neural crest cells causes Hirschsprung's disease (HD) and results in the development of cardiac outflow tract malformations. We hypothesize that the incidence of HD and bowel disorders associated with HD are increased in patients with hypoplastic left heart syndrome (HLHS) including left cardiac outflow tract obstruction.

Methods

All consecutive patients treated for HLHS at our institution during 1969 to 2005 were retrospectively reviewed. The number of patients with histologically confirmed HD or clinical findings characteristic of HD such as constipation and delayed meconium were recorded from the patient records.

Results

A total of 113 patients (65 males) were identified. At the time of survey, 57 patients (51%) were alive. Overall, there were 26 (23%) patients with constipation, and 9/23 (39%) had delayed passage of meconium after 48 hours. Despite frequent bowel disorders only 4 (3.5%) patients had undergone histologic examination of the rectum. Hirschsprung's disease was detected in 3 patients (95% confidence interval, 0.62-8.77). The expected number of HD cases in the study population was 0.026 giving 117-fold significant increase in the incidence of HD among patients with HLHS when compared to general Finnish population.

Conclusions

The incidence of HD is increased in patients with HLHS. These results point to a common neural crest-derived embryologic origin of HD and HLHS and warrant further studies.     

Ten-year outcome of patients with very small abdominal aortic aneurysm

BACKGROUND: The long-term fate of very small abdominal aortic aneurysms (AAA) is not well known. METHODS: Forty-one patients with asymptomatic small AAA (range 25 to 40 mm) underwent ultrasonographic surveillance. RESULTS: The median follow-up period was 7.3 years. The median linear aneurysm expansion rate was 2.0 mm/year (range 0 to 8.4). Three patients experienced aneurysm rupture (7.3%) which resulted in 1 patient'death. Thirteen patients underwent aneurysm repair (31.7%) and 1 patient died postoperatively (7.7%). The survival rate at 10-year follow-up was 59.0%. The survival rate free from aneurysm rupture and repair at 10-year follow-up was 69.9%. The median time for occurrence of aneurysm rupture was 4.9 years (range 1.8 to 10.5) and the need for aneurysm repair was 4.5 years (range 1.4 to 10.4). CONCLUSIONS: The fate of very small AAA is to slowly enlarge in size, sometimes threatening the patient's life. These observations underline the importance of continuous surveillance and the potential benefits of any medical treatment in this patient population.